Germicidal dips

ABSTRACT

IN GERMICIDAL DIPS, AND PARTICULARLY IN THE HYPOCHLORITE TREATMENT OF THE TEATS OF LACTATING ANIMALS FOR THE PREVENTION AND CONTROL OF MASTITTS, THE IMPROVEMENT THAT COMPRISES PROVIDING A SOLID LITHIUM HYPOCHLORITE CONCENTRATE CONTAINING ABOUT 10 TO 50% BY WEIGHT OF AVAILABLE CHLORINE, AND HAVING A MAXIMUM FREE HYDROXIDE EQUIVALENT TO ABOUT 3% LIOH AND PREFERABLY BELOW 0.5% BY WEIGHT, DISSOLVING SAID CONCENTRATE IN WATER JUST PRIOR TO USE IN PROPORTIONS TO PROVIDE ABOUT 1 TO 5% AND PREFERABLY ABOUT 4 TO 5% BY WEIGHT OF AVAILABLE CHLORIDE IN THE RESULTING SOLUTION, AND UTILIZING SUCH SOLUTION AS A GERMICIDAL DIP. AS A SPECIAL EMBODIMENT, PARTICULARLY FOR PREPARING GERMICIDAL DIPS FOR OTHER PURPOSES, WHERE AVAILABLE CHLORINE LEVELS OF ABOUT .01 TO 1% ARE DESIRED, THE COMPOSITION IS SUPPLIED WITH BUFFERING SAID REDUCING COMPONENTS TO BE COMBINED WITH THE LITHIUM HYPOCHLORITE WHEN PREPARING USE DILUTIONS THEREOF. THE REDUCING COMPONENT PROVIDES SLOW INACTIVATION OF SAID HYPOCHLORITE, AND THE AMOUNT OF REDUCING COMPONENT IS SUCH AS TO SUBSTANTIALLY INACTIVATE THE HYPOCHLORITE WITHIN A PRACTICAL TIME INTERVAL WHICH IS SUITABLY ABOUT 2 TO 6 TIMES THE GERMICIDAL CONTACT TIME INTENDED FOR SUCH USE DILUTION OR DIP.

United States Patent Ofiice 3,826,826 Patented July 30, 1974 3,826,826GERMICIDAL DIPS Abraham Cantor, Elkins Park, Pa., and Murray W.

Winicov, Flushing, N.Y., assignors to West Laboratories, Inc., LongIsland City, N.Y.

No Drawing. Continuation of abandoned applications Ser. No. 771,283,Oct. 28, 1968, and Ser. No. 856,191, Sept. 8, 1969. This applicationOct. 1, 1971, Ser. No.

Int. Cl. A61k 27/00 US. Cl. 424149 11 Claims ABSTRACT OF THE DISCLOSUREIn germicidal dips, and particularly in the hypochlorite treatment ofthe teats of lactating animals for the prevention and control ofmastitis, the improvement that comprises providing a solid lithiumhypochlorite concentrate containing about 10 to 50% by weight ofavailable chlorine, and having a maximum free hydroxide equivalent toabout 3% LiOH and preferably below 0.5% by weight, dissolving saidconcentrate in water just prior to use in proportions to provide about 1to and preferably about 4 to 5% by weight of avilable chloride in theresulting solution, and utilizing such solution as a germicidal dip.

As a special embodiment, particularly for preparing germicidal dips forother purposes, where available chlorine levels of about .01 to 1% aredesired, the composition is supplied with buffering and reducingcomponents to be combined with the lithium hypochlorite when preparinguse dilutions thereof. The reducing component provides slow inactivationof said hypochlorite, and the amount of reducing component is such as tosubstantially inactivate the hypochlorite within a practical timeinterval which is suitably about 2 to 6 times the germicidal contacttime intended for such use dilution or dip.

This application is a continuation of applications Ser. No. 856,191,filed Sept. 8, 1969 and Ser. No. 771,283, filed Oct. 28, 1968, both nowabandoned.

BACKGROUND OF THE INVENTION Mastitis has long been a major problem inthe dairy industry, with the disease being fostered and spread by theuse of high vacuum milking machines. For many years, it has been knownthat prevention and control of the disease requires great care in thesanitary treatment of the milking apparatus and animal hygiene. Theanimal treatment, as commonly practiced prior to the past few years, hadbeen essentially limited to washing the udders and teats with varioussanitizing solutions before the milking. Within the past ten years, andprimarily within the last few years, the importance of treating theteats after milking, by the use of germicidal solutions as teat dips,has been demonstrated to make an important contribution to the controlof mastitis. Two representative publications on this subject are Use ofSanitizers in Preventing Intra-Mammay Infections by C. K. Johns, Journalof Milk and Food Technology, 29: 3093l2, 1966 and Development ofEifective Teat DipsDisinfection of Teats, F. K. Neave et al., Nat. Inst.Res. Dairying, pp. 98-101, Report 1965. The latter publication isdescriptive of the use of liquid sodium hypochlorite, among otherproducts, as a source of available chlorine.

The currently commercial concentrated available hypochlorite productsare widely used as general purpose sanitizers and disinfectants, buthave not been found satisfactory when tested for use at dairymans levelsat teat dips. Calcium hypochlorite is commercially available as a powderwith a very high (70%) available chloride content. The powder dissolvesvery slowly, and it is virtually impossible to get hypochloritesolutions as high as 45% within any reasonable amount of time. Usingsolid calcium hypochlorite, there is a real danger of the undissolvedparticles adhering to the teat, causing chemical burns. Solid sodiumhypochlorite is extremely unstable and too dangerous for dairymen tostore and handle. Highly concentrated solutions of sodium hypochloritecontaining 10-15% available chlorine are available commercially, but arequite unstable with respect to maintaining their available chlorinecontent. It is not uncommon for such concentrated sodium hypochloritesolutions to lose half their strength in 2 or 3 months storage. The lossof available chlorine content is accelerated during the warm summermonths. Hypochlorite solutions containing 4-5% available chlorine,although more stable than the commercial 10-15% solutions, alsodeteriorate over a period of months; however, the loss during a one ortwo day period is insignificant.

THE INVENTION It has now been discovered that, in accordance with thepresent invention, the limitations in the preparation, marketing, farmlevel use, and eificacy of normally germicidal but non-irritatingsolutions of hypochlorite, as a post milking teat dip, can be eliminatedby employing stable, solid, powdered lithium hypochlorite compositions,for the preparation of 45% solutions of available chlorine, by simplesolution of readily soluble powders in water-such solutions then beingused directly. Commercial lithium hypochlorites in the form of drypowders containing 10 to 50% and preferably 30 to 40% by weight ofavailable chlorine, are quite stable and safe to store and handle.However, there is generally some free alkali as LiOH in commerciallithium hypochlorites, and this free alkali, calculated as LiOH, shouldbe kept below 3% and preferably below 0.5% by weight. The preferredrange value for the ratio of available chlorine to hydroxide (calculatedas LiOH) must not be less than 60. For this purpose, if one desires touse e.g. the commercially available lithium hypochlorite, known as LCALithium Hypochlorite (Lithcoa), the material may be dry blended with anamount of a suitable dry acidic substance, an acid phosphate, a solidbicarbonate, or the like, in an amount to react with the excess alkaliwhen the composition in dissolved in water. Alternatively, the freealkali can be controlled in the initial manufacture of the dry lithiumhypochlorite product, likewise providing a dry powdered material whichcan be easily stored and used by the dairyman. Accordingly, by preparingteat dip solutions in the amounts needed shortly prior to use, thedairyman is assured of having solutions essentially free of componentswhich can cause irritation to the teats. Commercial lithium hypochloritemay contain varying amounts of other components in addition to LiOCl andLiOH, such as, for example, Li CO LiClO LiCl, NaCl, Na SO K S0representing both indigenous ingredients and solid dilucuts. Thepresence of such salts is not objectionable.

The following tabulation will indicate the general and preferred rangeof components such as may characterize lithium hypochlorite productssuitable for use in teat dips:

As typical of hypochlorites, one atom of chlorine in the plus one stateis equivalent to two atoms of elemental chlorine (zero"), since both arereduced to chloride (01-, minus one). Thus, from the standpoint ofchlorine activity, each part by weight of LiO Cl is equivalent to about1.22 parts by weight of available chlorine.

If-a-commercial product were found" to be generally appropriate, butshowed a free alkali (LiOH) content greater than 3% or otherwise higherthan the alkali level desired as maximum in the product, the amount ofsolid acidic material to beadded to counteract the excess alkali couldreadily be determined. If sodium bicarbonate, for example, is used asthe acidic material, one would blend with the solid commercialhypochlorite 3.5 parts by weight of sodium bicarbonate per hundred partsper weight of the commercial hypochlorite for each 1% of excess alkali(calculated as LiOH) to be neutralized.

The following examples showing the preparation of typical teat dipsolutions in accordance with the present invention will provide a fullerunderstanding of the inven tion, but it is to be understood that theseexamples are given by way of illustration and not of limitation.

Example I A commercial lithium hypochlorite powder is procured havingthe following analysis:

Component Percent by weight LiOCl 30 NaCl 34 NflgSO; K SO "i LiCl 3LiClO 3 LiOH 2 Li CO 1 H O 7 This product, providing about 35% by weightavailable chlorine, and having an LiOH content below 3%, is suitable foruse in preparing and disinfecting solutions. By adding 460 grams of thispowder to an empty one-gallon container, filling the container to theone-gallon level with tap water, and stirring the contents for about 60seconds, a clear solution is obtained containing approximately 4% byweight available chlorine and suitable for use as a teat dip.

If other available chlorine concentrations are desired, it is simplynecessary to vary the amount of powder. Thus, for example, 580 grams ofthe powder diluted to one gallon with tap water provides a teat dipsolution containing about 5% by weight available chlorine; and fourounces of the powder diluted to one gallon with tap water provides asolution containing approximately 1% by weight available chlorine.

Example II Having at hand the lithium hypochlorite powder described inExample I, it is desired that the effective free alkali (calculated asLiOH) be reduced to about 0.5% by weight. In order to accomplish this,100 parts by weight of the powder and 5.25 parts by weight of sodiumbicarbonate are dry blended to provide a uniform mixture. This mixture,when dissolved in Water at the rate of 485 grams diluted to one gallonwith water, provides a solution containing 4% by weight of availablechlorine and approximately .06% by weightof free alkali (calculated asLiOH).

This modified powder can be readily dissolved in water in appropriateamounts as described in Example I to provide teat dip solutions whichare entirely safe from the standpoint of free alkali present in suchsolutions.

When preparing germicidal clips for other purposes, as for example forcold sterilization of instruments, rubber articles, fabrics and otheritems sensitive to chlorine the quantity of lithium hypochlorite usedwill generally be an amountto provide about 0.01 to 1% availablechlorine in a use dilution, i.e., 100 to 10,000 p.p.m. of availablechlorine. In treating such chlorine sensitive materials and articles aneffective germicidal or sporicidal treatment, depending on the availablechlorine concentrate may range from about 5 minutes to 2 hours, and itis desirable to remove such materials and articles from the chlorinesolution at the end of such treatment period in order to minimize damagedue to more prolonged contact with the chlorine. It is frequentlyimpossible or inconvenient, however, to provide for such timely removalof items from a treatment solution.

As a means for minimizing damage which can thus result to chlorinesensitive items, it is desirable to formulate the germicidal orsporicidal use dilution with reducing components to provide a controlleddestruction of the hypochlorite and available chlorine within apractical time interval which may be of the order of 2 to 6 times theactive contact period desired for the particular germicidal dip.

Buffering agent is suitably present to provide a controlled pH in theuse dilution generally within the range of pH 4 to pH 10. Typicalbuffering agents which can be employed include Buffer Approx. pH Sodiumbicarbonate 8-'l0 Sodium citrate 47 Sodium Phosphate (mixtures ofminoand di-salts) Selection of optimum pH can be influenced by theselection of reducing agent as hereinafter described. The optimum pHwill also vary from one situation to another depending on the type andpH sensitivity of the articles being treated, and the type germicidaland/or sporicidal action desired.

The reducing agent should be an organic compound containing 1 to 6carbon atoms in which each carbon atom is either oxidized itself orjoined to a carbon which is oxidized to form a grouping selected fromthe class consisting of COOX, CHO, --'CH O'H, and =C'=O, where X is H ora salt forming cation. Typical reducing agents falling within this classinclude: formic acid, oxalic acid, tartaric acid, lactic acid, gluconoicacid, citric acid, glycerine, acetaldehyde, formaldehyde, and acetone.

The amount of reduing agent should be within the range of about 0.01 to5% w./v. based on the use dilution, with the actual amount beinggenerally proportioned to the amount of hypochlorite. Buffering agent ispresent only in the amount required to maintain the desired pH withinthe range pH 410. This will generally be within the range of about 0.01to 1% W./v. based on the use dilution.

Depending on the specific amount of available chlorine needed for thegermicidal or sterilizing purpose, and the specific safety factorrequired, the chlorine disappearance time can be set in the followingmanner.

A quantity of hypochlorite is dissolved in water and the pH is adjustedbetween the range 410, as desired, using appropriate buffering agent. Aquantity of organic reducing substance is then added. Portions of thesolution are then Withdrawn periodically, and juenched with an excess ofpotassium iodide and acetic acid, thereby generating an equivalentamount of iodine Which can be titrated with thiosulfate. From theprofile of available chlorine vs. time thus obtained, the proper amountof organic reducing substance for the intended purpose can bedetermined.

In considering the several variables which affect the available chlorinecontent of the solutions, it must be recognized that the reaction rateis ordinarily a function of the concentration of available chlorine andthe reducing agent, and may also be dependent on the pH. Temperature isalso a factor With increase in temperature tending to shorten both thegermicidal action and chlorine disappearance time. Thus productspresented for particular germicidal dip uses should carry indicationsconcerning both the intended use dilution and the approximatetemperature for each use dilution.

Due to the inherent reactivity of the hypochlorite and reducing agent itis essential that these components be brought together only when one isready to prepare a use dilution. Commercial products will thereforegenerally be presented as two component systems with an amount ofhypochlorite and the appropriate amount of reducing and butferingcomponents separated one from the other by various conventional means.

Thefollowing Examples will aid in a better understanding of thegermicidal dip compositions containing reducing and bulferingcomponents, but it is to be understood that these Examples are given byway of illustration and not of limitation.

Example 111 One gram of commercial lithium hypochlorite, about 0.2 gramof a phosphate butter mixture, and 0.5 gram of sodium formate werediluted in 100 ml. of water to provide a solution initially containing350 p.p.m. available chlorine and having a pH of 6.7. The availablechlorine content was determined periodically, and is given below.

P.p.m. Available Chlorine as a Function of Time Time, minutes [P.pm. Av.Cl. 350

In separate experiments, the same ingredients, diluted in the samemanner, were found to be both germicidal and sporicidal, and inaddition, were devoid of chlorine in 90 minutes.

Example IV In a series of separate experiments, 1.25 grams of lithiumhypochlorite, about 0.3 gram of a phosphate buffer mixture, and 0.5 gramof the reducing substances indicated below, were diluted in 100 ml.water at 25 C. to provide a solution initially containing 438 ppm.available chlorine and having a pH of 6.7. The available chlorine as afunction of time is given below.

P.P.M. AVAILABLE CHLORINE AS A FUNCTION OF TIME Parts per millionReducing agent 0 min. min. 30 min. 60 min. 90 min:

Sodium citrate 438 166 31 1 Sodium oxalate 438 326 89 24 1 Sodiumtartrate 438 398 300 Sodium glueonate- 438 392 Glycerine 438 417 394 343280 Example V In order to demonstrate the eifect of pH on the rate ofchlorine loss, additional preparations were made employing 1.25 grams ofcommercial lithium hypochlorite, about 0.5 gram of a buffer mixture, and0.5 gram of reducing substance, diluted in 100 ml. water at 25 C. toprovide a solution initially containing 438 ppm. available chlorim andhaving the pH indicated below. The results after 10 minutes are given.

The above results indicate that while the performance of sodium citrateis not improved significantly in lowering the pH from 6.7 to 4.7 (seeprevious Example), the sodium oxalate performance is significantlyimproved. Likewise, acetone is unsuitable for the purpose of thisinvention at pH 6.7, but is suitable at higher pH. Glycerine was notimproved in moving from pH -6.7 to 4.7, and sodium formate was renderedslower acting by the same pH change.

Various changes and modifications in the compositions and proceduresherein described for providing improved germicidal dip solutions willoccur to those skilled in the art, and to the extent that such changesand modifications are embraced by the appended claims, it is to beunderstood that they constitute part of the present invention.

We Claim:

1. A composition for use in preparing teat dip solutions for theprevention and control of mastitis consisting essentially of drypowdered lithium hypochlorite concentrate in an amount sufficient toprovide about 10 to 50% by weight of available chlorine and containinglithium hydroxide as an impurity; and, a dry substance of acidicreaction in the presence of hydroxide ion selected from the groupconsisting of acid phosphates and solid bicarbonates, said dry acidicsubstances being present in an amount such that the maximum freehydroxide available is equivalent to about 3% by weight of LiOH.

2. A composition as defined in claim 1 wherein the effective amount offree hydroxide is less than about 0.5% by weight when calculated asLiOH, and in which the ratio of available chlorine to free hydroxide,calculated as LiOH, is not less than 60.

3. A composition as defined in claim 1 wherein the available chlorine isin the range of about 30 to 40% by weight.

4. A composition as defined in claim 1 wherein said dry substance ofacidic reaction in the presence of hydroxide ion is a bicarbonate.

5. A dry composition for use in preparing hypochloritecontaininggermicidal solutions, said composition com prising commercial lithiumhypochlorite in which free hydroxide present as impurity does not exceedthe equivalent of 3% by weight of LiOH, said commercial lithiumhypochlorite containing about 10% to 50% by weight available chlorineand present in an amount suflicient to provide about 0.01 to 1%available chlorine in a use dilution; an organic compound functioning asa reducing agent in the presence of the highly oxidizing hypochloriteradical, said organic compound being a C to C compound wherein eachcarbon atom is oxidized, or is joined to a carbon atom which isoxidized, to form a grouping selected from the class consisting of COOX,-OHO, CH OH, and =C=O wherein X is H or a salt-forming cation, saidreducing agent being present in an amount suflicient to provide about0.01 to 5% w./v. based upon the volume of said use dilution; and, abuffering agent present in an amount sufiicient to provide a controlledpH of said use dilution of about pH 4 to pH 10.

6. A composition as defined in claim 5 wherein the organic compoundfunctioning as a reducing agent is maintained separate from the lithiumhypochlorite prior to preparation of such use dilution.

7. A composition as defined in claim 5 wherein the reducing andbuifering agents are maintained separate from the lithium hypochloriteprior to preparation of such use dilution.

8. A composition as defined in claim 5 wherein the organic compoundfunctioning as a reducing agent is oxalic acid or a salt thereof.

9. A composition as defined in claim 5 wherein the organic compoundfunctioning as a reducing agent is citric acid or a salt thereof.

10. A composition as defined in claim 5 wherein the organic compoundfunctioning as a reducing agent is formic acid or a salt thereof.

11. A composition as defined in claim 5 wherein the lithiumhypochlorite, the organic compound functioning as a reducing agent, andbuffering agent are all present as solid substances.

References Cited UNITED STATES PATENTS OTHER REFERENCES Yearbook ofAgriculture (1956), Animal Diseases, pp. 248 and 249.

SAM ROSEN, Primary Examiner

